In High-Risk Patients, Most DOACs Reduce Stroke Risk Without Increasing Bleeding Risk vs Warfarin

New data is providing clinicians with an overview of the stroke and bleeding risk associated with direct oral anticoagulants in patients with atrial fibrillation (AF) and high risk of gastrointestinal bleeding.

A subgroup analysis of the ARISTOPHANES study, the analysis used propensity score-matching to compare risks of stroke and major bleeding for rivaroxaban, apixaban, and dabigatran against warfarin and one another in the aforementioned patient population.

“This is one of the first real-world studies to compare NOACs in the patients with NVAF and high risk of GI bleed; the results may help inform decision-making regarding OACs in this high-risk patient population,” wrote investigators.

With the role of direct oral anticoagulants (DOACs) in nonvalvular AF outlined in guidelines, focus in research has begun to shift from clinical trials to real-world settings. With this in mind, a team of investigators from the US and Europe carried out the current study with the intent of assessing potential differences in efficacy and safety profile among DOACs compared to warfarin in patients at increased risk of gastrointestinal bleeding.

Investigators designed their study as a subgroup analysis of the ARISTOPHANES study, which was a retrospective cohort study that contained data from the CMS Medicare database and 4 commercial claims databases from January 1, 2013-September 30, 2015. Using the study, investigators identified a cohort of more than 375,000 patients for inclusion in their analyses.

For inclusion, patients were required to have nonvalvular AF and at least 1 gastrointestinal risk factor. Gastrointestinal risk factors included being 75 years of age or older, stage 3-5 CKD, an HAS-BLED score of 3 or greater, prior use of corticosteroids, antiplatelets, or NSAIDs, or history of gastrointestinal bleed or ulcer.

Ultimately, 381,054 patients were identified for inclusion in the current study. The most common high-risk bleeding factors was a HAS-BLED score of 3 or more (n=284,527), being aged 75 years or older (n=252,835), medication history (n=107,675), prior gastrointestinal bleeding conditions (n=74,818), and stage 3-5 chronic kidney disease (n=56,892).

Of the 381,054 included, 89,296 were prescribed apixaban, 28,317 were prescribed dabigatran, 118,378 were prescribed rivaroxaban, and 145,063 were prescribed warfarin. Investigators noted patients prescribed edoxaban were not included in the study because of an insufficient sample size. Using data obtained from the ARISTOPHANES study, investigators created 6 propensity score-matched cohorts to compare incidence of stroke and/or systemic embolism and bleeding events using Cox models.

Upon analysis, results suggested all DOACs examined in the study were associated with avower risk of stroke and/or systemic embolism than warfarin, with reductions in risk of 40% (HR, 0.60; 95% CI, 0.52-0.68), 25% (HR, 0.75; 95% CI, 0.64-0.88), and 21% (HR, 0.79; 95% CI, 0.73-0.86) for apixaban, dabigatran, and rivaroxaban, respectively. When assessing risk of major bleeding, results suggested apixaban (HR, 0.59; 95% CI, 0.56-0.63) and dabigatran (HR, 0.78; 95% CI, 0.70-0.86) were associated with a lower risk of major bleeding compared to warfarin, but an increased risk was observed with rivaroxaban (HR, 1.11; 95% CI, 1.05-1.16).

Investigators also pointed out analyses were performed comparing DOACs against one another. These results suggested patients taking apixaban had a lower stroke and/or systemic embolism risk compared to those taking dabigatran (HR, 0.75; 95% CI, 0.62-0.91) and rivaroxaban (HR, 0.74; 95% CI, 0.67-0.83) and those taking dabigatran had a similar risk of stroke and/or systemic embolism compared to those thing rivaroxaban (HR, 1.12; 95% CI, 0.95-1.33).

Additionally, apixaban was associated with a lower risk of major bleeding and lower risk of gastrointestinal bleeding when compared against dabigatran (HR for major bleeding, 0.74 [95% CI, 0.62-0.88]; HR for gastrointestinal bleeding, 0.64 [95% CI,0.50-0.81]) and rivaroxaban (HR for major bleeding, 0.55 [95% CI, 0.52-0.58]; HR for gastrointestinal bleeding, 0.47 [95% CI, 0.43-0.51]). Further analysis indicated dabigatran was associated with lower risk of major bleeding (HR, 0.73; 955 CI, 0.66-0.80) and gastrointestinal bleeding (HR, 0.77; 95% CI, 0.67-0.87) than rivaroxaban.

“To our knowledge, this is the largest and one of the first real-world studies to compare NOACs with warfarin among patients with NVAF population and high risk of GI bleed. In this subgroup analysis of the ARISTOPHANES study, NOACs were associated with lower risk of stroke and/or SE compared with warfarin use among patients with NVAF and high risk of GI bleeding,” wrote investigators.

This study, “Oral Anticoagulants for Nonvalvular Atrial Fibrillation in Patients With High Risk of Gastrointestinal Bleeding,” was published in JAMA Network Open.